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<p>Despite lacking melanin, vitiligo skin paradoxically exhibits a lower incidence of non-melanoma skin cancers, indicating alternative epidermal defense mechanisms. We investigated the protective role of microRNA-31-5p (miR-31-5p), which is elevated in vitiligo lesions, against UV-B-induced DNA damage in keratinocytes. Primary human keratinocytes exposed to UV-B were treated with miR-31-5p mimic or antagomiR. miR-31-5p mimic significantly reduced DNA damage and increased the expression of nucleotide excision repair genes (DDB1, ERCC2, XPC), while alleviating replication stress. SP1 was identified as a direct target of miR-31-5p, and its suppression mirrored the DNA-protective effects. Importantly, miR-31-5p mimic robustly activated autophagy, as shown by increased expression of autophagy markers and enhanced autophagic flux; bafilomycin treatment further elevated LC3B and Beclin levels, indicating augmented autophagosome accumulation. Inhibition of autophagy with a ULK1 inhibitor abrogated the DNA-protective effects mediated by miR-31-5p mimic, confirming autophagy’s essential role. Analysis of lesional vitiligo epidermis revealed elevated miR-31-5p and reduced SP1 expression, consistent with <i>in vitro</i> findings. Our study identifies a novel miR-31-5p–SP1–autophagy–DNA repair axis in UV-B-exposed keratinocytes, providing new insight into melanin-independent epidermal protection in vitiligo and potential therapeutic strategies for enhancing UV resistance.</p>

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microRNA miR-31-5p confers protection to melanin-deficient vitiligo keratinocytes against UV-B induced DNA damage by activating autophagy machinery

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月2日

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  • Manish Chowdhary,
  • Arun Raina,
  • Anshu Priya,
  • Akta Kundu,
  • Aayush Gupta,
  • Archana Singh

摘要

Despite lacking melanin, vitiligo skin paradoxically exhibits a lower incidence of non-melanoma skin cancers, indicating alternative epidermal defense mechanisms. We investigated the protective role of microRNA-31-5p (miR-31-5p), which is elevated in vitiligo lesions, against UV-B-induced DNA damage in keratinocytes. Primary human keratinocytes exposed to UV-B were treated with miR-31-5p mimic or antagomiR. miR-31-5p mimic significantly reduced DNA damage and increased the expression of nucleotide excision repair genes (DDB1, ERCC2, XPC), while alleviating replication stress. SP1 was identified as a direct target of miR-31-5p, and its suppression mirrored the DNA-protective effects. Importantly, miR-31-5p mimic robustly activated autophagy, as shown by increased expression of autophagy markers and enhanced autophagic flux; bafilomycin treatment further elevated LC3B and Beclin levels, indicating augmented autophagosome accumulation. Inhibition of autophagy with a ULK1 inhibitor abrogated the DNA-protective effects mediated by miR-31-5p mimic, confirming autophagy’s essential role. Analysis of lesional vitiligo epidermis revealed elevated miR-31-5p and reduced SP1 expression, consistent with in vitro findings. Our study identifies a novel miR-31-5p–SP1–autophagy–DNA repair axis in UV-B-exposed keratinocytes, providing new insight into melanin-independent epidermal protection in vitiligo and potential therapeutic strategies for enhancing UV resistance.